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Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / bone marrow chromosome aberration
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions (limited documentation, no data on test substance purity).

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1974
Report Date:
1974

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 475 (Mammalian Bone Marrow Chromosome Aberration Test)
Deviations:
yes
Remarks:
- only male animals; only three animals in negative control group; only 500 cells evaluated for mitotic index; no bone marrow toxicity in highest concentration used
GLP compliance:
no
Type of assay:
chromosome aberration assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): synthetic silica sodium silicoaluminate (FDA 71-45)
- Physical state: fine white powder
- Analytical purity: no data

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 10-12 weeks
- Weight at study initiation: 300 to 350 g
- Housing: Rats were housed one to five per cage.
- Diet (e.g. ad libitum): commercial 4 % fat diet; periodic tests to verify the absence of coliforms, Salmonella and Pseudomonas sp. were performed.
- Water (e.g. ad libitum): water; 2 times per week water was changed
- Quarantine: 4 to 11 days
- Others: Animals were identified by ear punch. Sanitary cages and bedding were changed two times per week.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
saline (0.85 %)
Duration of treatment / exposure:
acute study: single dose (post exposure period: up to 48 hours)
subacute study: five days
Frequency of treatment:
acute study: single dose
subacute study: 5 doses, daily
Post exposure period:
acute study: sampling times 6, 24 and 48 h after administration of test substance
subacute study: animals were sacrificed 6 hours after the last dose
Doses / concentrations
Remarks:
Doses / Concentrations:
acute + subacute: 4.25, 42.5, 425 mg/kg bw
Basis:
nominal conc.
No. of animals per sex per dose:
5; only 3 animals in negative control group
acute study: 59
subacute study: 18
Control animals:
yes, concurrent vehicle
Positive control(s):
0.3 mg/kg triethylene melamine (TEM) administered intraperitoneally

Examinations

Tissues and cell types examined:
freshly isolated bone marrow cells
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION:
The dose of 425 mg/kg corresponds to the LD5.

DETAILS OF SLIDE PREPARATION: Fixed cells were dropped on slides and dried. Slides were stained using a 5% Giemsa solution, subsequently rinsed with acetone/xylene and placed in xylene for 30 min before counting.

METHOD OF ANALYSIS:
Duplicate slides were examined microscopically. Only diploid cells were analyzed.

OTHER: 2 h prior to killing, each animal was given 4 mg/kg of colcemid intraperitoneally.
Evaluation criteria:
no data
Statistics:
no data

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
yes
Remarks:
LD5 = 425 mg/kg
Vehicle controls validity:
valid
Negative controls validity:
not examined
Positive controls validity:
valid
Additional information on results:
The compound produced no detectable significant aberration of the bone marrow metaphase chromosomes of rats when administered orally at the tested dosage levels. The test compound can be considered non-mutagenic.

Any other information on results incl. tables

acute study: The negative controls and the 3 compound-treated groups were within the normal limits of breaks observed (0 -3 %). The mitotic indices were in good agreement except for the 425 mg/kg group which was slightly, but not significantly, depressed. In the positive control group 5 % of the cells with severe damage (> 10 aberrations/cell) and 1% of the cells with pulverized chromosomes were observed.

Dose [mg/kg]

Sampling time [h]

Mitotic index [%]

Cells with aberrations [%]

0 (saline)

6

10

2

24

11

3

48

9

3

4.25

6

11

2

24

11

1

48

11

3

42.5

6

8

0

24

9

1

48

10

0

425

6

12

2

24

6

0

48

10

2

TEM 0.3

48

3

48

subacute study: The negative control groups and the three treated groups were within normal limits for breaks and mitotic indices.

Dose [mg/kg]

Mitotic index [%]

Cells with aberrations [%]

0 (saline)

8

3

4.25

10

2

42.5

11

2

425

8

3

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative